Pesticidal 5-substituted-oxyalkylamino-1-arylpyrazole derivatives

ABSTRACT

The invention relates to 5-sub-stituted-oxyalkylaminopyrazole derivatives of the formula 
                         
or salts thereof wherein the various symbols are as defined in the description, to processes for their preparation, to compositions thereof, and to their use for the control of pests including arthropods and helminths.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is the U. S. national stage of InternationalApplication No. PCT/EP2004/009378, filed Aug. 21, 2004 and claimspriority under 35 U.S.C. §119 of Application No. 03019618.2, filed inthe European Patent Office on Sep. 4, 2003.

The invention relates to novel 5-substituted-oxyalkylaminopyrazolederivatives, processes for their preparation, to compositions thereof,and to their use for the control of pests (including arthropods andhelminths).

The control of insects, arachnids and helminths with 1-arylpyrazolecompounds has been described in, for example, patent publication numbersWO 87/03781, EP 0295117, U.S. Pat. No. 5,556,873, U.S. Pat. No.4,771,066 and WO 02/066423.

However, since modern pesticides must meet a wide range of demands, forexample regarding level, duration and spectrum of action, use spectrum,toxicity, combination with other active substances, combination withformulation auxiliaries or synthesis, and since the occurrence ofresistances is possible, the development of such substances can never beregarded as concluded, and there is constantly a high demand for novelcompounds which are advantageous over the known compounds, at least asfar as some aspects are concerned.

It is an object of the present invention to provide new pesticides whichmay be used in domestic companion animals.

It is advantageous to apply pesticides to animals in oral form so as toprevent the possible contamination of humans or the surroundingenvironment.

Another object of the invention is to provide new pesticides which maybe used in lower dose than existing pesticides.

Another object of the invention is to provide new pesticides which aresubstantially non-emetic.

Another object of the invention is to provide new pesticides which aresafer to the user and the environment.

These objects are met in whole or in part by the present invention.

The present invention provides a compound which is a5-substituted-oxyalkylaminopyrazole derivative of formula (I):

wherein:

-   R¹ is CN, CSNH₂ or C(═N—Z)—S(O)₁Q;-   Z is H, (C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl, (C₃-C₆)-alkenyl,    (C₃-C₆)-alkynyl, —(CH₂)_(q)R⁷, COR⁸, CO₂—(C₁-C₆)-alkyl or    S(O)_(p)R⁸;-   Q is (C₁-C₆)-alkyl or CH₂R⁷;-   W is C-halogen, C—CH₃ or N;-   R² is hydrogen, halogen or CH₃;-   R³ is (C₁-C₃)-haloalkyl, (C₁-C₃)-haloalkoxy or SF₅;-   R⁴ is hydrogen, (C₂-C₆)-alkenyl, (C₂-C₆)-haloalkenyl,    (C₂-C₆)-alkynyl, (C₂-C₆)-haloalkynyl, (C₃-C₇)-cycloalkyl,    (C₃-C₇)-cycloalkyl-(C₁-C₆)-alkyl, CO₂—(C₁-C₆)-alkyl,    CO₂—(C₃-C₆)-alkenyl, CO₂—(C₃-C₆)-alkynyl, CO₂—(CH₂)_(m)R⁷ or SO₂R⁸;    or-   (C₁-C₆)-alkyl unsubstituted or substituted by one or more radicals    selected from the group consisting of halogen, (C₁-C₆)-alkoxy,    (C₁-C₆)-haloalkoxy, (C₃-C₆)-alkenyloxy, (C₃-C₆)-haloalkenyloxy,    (C₃-C₆)-alkynyloxy, (C₃-C₆)-haloalkynyloxy, (C₃-C₇)-cycloalkyl,    S(O)_(p)R⁸, CN, NO₂, OH, COR⁹, NR⁹R¹⁰, S(O)_(p)R⁷, OR⁷ and CO₂R⁹;-   A is (C₁-C₆)-alkylene or (C₁-C₆)-haloalkylene;-   X is C(═O), C(═S) or SO₂;-   Y is O, NR¹¹ or a covalent bond;-   R⁵ is (C₃-C₆)-alkenyl, (C₃-C₆)-haloalkenyl, (C₃-C₆)-alkynyl,    (C₃-C₆)-haloalkynyl, (C₃-C₇)-cycloalkyl,    (C₃-C₇)-cycloalkyl-(C₁-C₆)-alkyl, —CH₂)_(q)R7 or —CH₂)_(q)R¹²; or is    (C₁-C₆)-alkyl unsubstituted or substituted by one or more radicals    selected from the group consisting of halogen, (C₁-C₆)-alkoxy,    (C₁-C₆)-haloalkoxy, (C₃-C₆)-alkenyloxy, (C₃-C₆)-haloalkenyloxy,    (C₃-C₆)-alkynyloxy, (C₃-C₆)-haloalkynyloxy, (C₃-C₇)-cycloalkyl,    S(O)_(p)R⁸, CN, NO₂, OH, COR⁹, NR⁹R¹⁰, S(O)_(p)R⁷, OR⁷ and CO₂R⁹;-   R⁶ is (C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl, (C₂-C₆)-alkenyl,    (C₂-C₆)-haloalkenyl (C₂-C₆)-alkynyl or (C₂-C₆)-haloalkynyl;-   R⁷ is phenyl unsubstituted or substituted by one or more radicals    selected from the group consisting of halogen, (C₁-C₆)-alkyl,    (C₁-C₆)-haloalkyl, (C₁-C₆)-alkoxy, (C₁-C₆)-haloalkoxy, CN, NO₂,    S(O)_(p)R⁸, COR¹⁰, COR¹³, CONR⁹R¹⁰, SO₂NR⁹R¹⁰, NR⁹R¹⁰ and OH;-   R⁸ is (C₁-C₆)-alkyl or (C₁-C₆)-haloalkyl;-   R⁹ and R¹⁰ are each independently H, (C₁-C₆)-alkyl,    (C₁-C₆)-haloalkyl, (C₃-C₆)-alkenyl, (C₃-C₆)-haloalkenyl,    (C₃-C₆)-alkynyl, (C₃-C₆)-cycloalkyl or    —(C₁-C₆)-alkyl-(C₃-C₆)-cycloalkyl; or-   R⁹ and R¹⁰ together with the attached N atom form a five- or    six-membered saturated ring which optionally contains an additional    hetero atom in the ring which is selected from O, S and N, the ring    being unsubstituted or substituted by one or more radicals selected    from the group consisting of halogen, (C₁-C₆)-alkyl and    (C₁-C₆)-haloalkyl;-   R¹¹ is H, (C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl, (C₃-C₆)-alkenyl or    (C₃-C₆)-alkynyl;-   R¹² is heterocyclyl unsubstituted or substituted by one or more    radicals selected from the group consisting of halogen,    (C₁-C₄)-alkyl, (C₁-C₄)-haloalkyl, (C₁-C₄)-alkoxy,    (C₁-C₄)-haloalkoxy, NO₂, CN, CO₂(C₁-C₆)-alkyl, S(O)_(p)R⁸, OH and    oxo;-   R¹³ is phenyl unsubstituted or substituted by one or more radicals    selected from the group consisting of halogen, (C₁-C₆)-alkyl,    (C₁-C₆)-haloalkyl, (C₁-C₆)-alkoxy, (C₁-C₆)-haloalkoxy, CN, NO₂,    S(O)_(p)R⁸ and NR⁹R¹⁰;-   n, p and r are each independently zero, one or two;-   m and q are each independently zero or one; and-   each heterocyclyl in the above-mentioned radicals is independently a    heterocyclic radical having 3 to 7 ring atoms and 1, 2 or 3 hetero    atoms in the ring selected from the group consisting of N, O and S;-   or a pesticidally acceptable salt thereof.

These compounds possess valuable pesticidal properties.

The invention also encompasses any stereoisomer, enantiomer or geometricisomer, and mixtures thereof.

By the term “pesticidally acceptable salts” is meant salts the anions orcations of which are known and accepted in the art for the formation ofsalts for pesticidal use. Suitable salts with bases, e.g. formed bycompounds of formula (I) containing a carboxylic acid group, includealkali metal (e.g. sodium and potassium), alkaline earth metal (e.g.calcium and magnesium), ammonium and amine (e.g. diethanolamine,triethanolamine, octylamine, morpholine and dioctylmethylamine) salts.Suitable acid addition salts, e.g. formed by compounds of formula (I)containing an amino group, include salts with inorganic acids, forexample hydrochlorides, sulphates, phosphates and nitrates and saltswith organic acids for example acetic acid.

In the present specification, including the accompanying claims, theaforementioned substituents have the following meanings:

Halogen atom means fluorine, chlorine, bromine or iodine.

The term “halo” before the name of a radical means that this radical ispartially or completely halogenated, that is to say, substituted by F,Cl, Br, or I, in any combination, preferably by F or Cl.

Alkyl groups and portions thereof (unless otherwise defined) may bestraight- or branched-chain.

The expression “(C₁-C₆)-alkyl” is to be understood as meaning anunbranched or branched hydrocarbon radical having 1, 2, 3, 4, 5 or 6carbon atoms, such as, for example a methyl, ethyl, propyl, isopropyl,1-butyl, 2-butyl, 2-methylpropyl or tert-butyl radical.

Alkyl radicals and also in composite groups, unless otherwise defined,preferably have 1 to 4 carbon atoms.

“(C₁-C₆)Haloalkyl” means an alkyl group mentioned under the expression“(C₁-C₆)alkyl” in which one or more hydrogen atoms are replaced by thesame number of identical or different halogen atoms, such asmonohaloalkyl, perhaloalkyl, CF₃, CHF₂, CH₂F, CHFCH₃, CF₃CH₂, CF₃CF₂,CHF₂CF₂, CH₂FCHCl, CH₂Cl, CCl₃, CHCl₂ or CH₂CH₂Cl.

The expression “(C₁-C₆)-alkylene” is to be understood as meaning anunbranched or branched chain alkanediyl group having from 1 to 6 carbonatoms, according to the IUPAC Nomenclature of Organic Chemistry 1979,for example —CH₂—, —CH₂CH₂—, —CH₂CH₂CH₂— or —CH₂CH(CH₃)—.

The expression “(C₁-C₆)-haloalkylene” is to be understood to mean analkylene group mentioned under the expression “(C₁-C₆)-alkylene”, inwhich one or more hydrogen atoms are replaced by the same number ofidentical or different halogen atoms.

“(C₁-C₆)Alkoxy” means an alkoxy group whose carbon chain has the meaninggiven under the expression “(C₁-C₆)alkyl”. “Haloalkoxy” is, for example,OCF₃, OCHF₂, OCH₂F, CF₃CF₂O, OCH₂CF₃ or OCH₂CH₂Cl.

“(C₂-C₆)Alkenyl” means an unbranched or branched non-cyclic carbon chainhaving a number of carbon atoms which corresponds to this stated rangeand which contains at least one double bond which can be located in anyposition of the respective unsaturated radical. “(C₂-C₆)Alkenyl”accordingly denotes, for example, the vinyl, allyl, 2-methyl-2-propenyl,2-butenyl, pentenyl, 2-methylpentenyl or the hexenyl group.

“(C₂-C₆)Alkynyl” means an unbranched or branched non-cyclic carbon chainhaving a number of carbon atoms which corresponds to this stated rangeand which contains one triple bond which can be located in any positionof the respective unsaturated radical. “(C₂-C₆)Alkynyl” accordinglydenotes, for example, the propargyl, 1-methyl-2-propynyl, 2-butynyl or3-butynyl group.

Cycloalkyl groups preferably have from three to seven carbon atoms inthe ring and are optionally substituted by halogen or alkyl.

In compounds of formula (I) the following examples of radicals areprovided:

-   An example of alkyl substituted by cycloalkyl is cyclopropylmethyl;-   an example of alkyl substituted by alkoxy is methoxymethyl    (CH₃0CH₂—); and-   an example of alkyl substituted by alkylthio is methylthiomethyl    (CH₃SCH₂—).

A “heterocyclyl” group can be saturated, unsaturated or heteroaromatic;it preferably contains one or more, in particular 1, 2 or 3, heteroatoms in the heterocyclic ring, preferably selected from the groupconsisting of N, O and S; it is preferably an aliphatic heterocyclylradical having 3 to 7 ring atoms or a heteroaromatic radical having 5 to7 ring atoms. The heterocyclic radical can be, for example, aheteroaromatic radical or ring (heteroaryl) such as, for example, amono-, bi- or polycyclic aromatic system in which at least 1 ringcontains one or more hetero atoms, for example pyridyl, pyrimidinyl,pyridazinyl, pyrazinyl, triazinyl, thienyl, thiazolyl, thiadiazolyl,oxazolyl, isoxazolyl, furyl, pyrrolyl, pyrazolyl, imidazolyl andtriazolyl, or it is a partially or fully hydrogenated radical such asoxiranyl, oxetanyl, oxolanyl (=tetrahydrofuryl), oxanyl, pyrrolidyl,piperidyl, piperazinyl, dioxolanyl, oxazolinyl, isoxazolinyl,oxazolidinyl, isoxazolidinyl and morpholinyl. The “heterocyclyl” groupmay be unsubstituted or substituted, preferably by one or more radicals(preferably 1, 2 or 3 radicals) selected from the group consisting ofhalogen, alkoxy, haloalkoxy, alkylthio, hydroxyl, amino, nitro,carboxyl, cyano, alkoxycarbonyl, alkylcarbonyl, formyl, carbamoyl, mono-and dialkylaminocarbonyl, substituted amino such as acylamino, mono- anddialkylamino, and alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl,haloalkylsulfonyl, alkyl and haloalkyl, and additionally also oxo. Theoxo group can also be present at those hetero ring atoms where variousoxidation numbers are possible, for example in the case of N and S.

The term pests means arthropod pests (including insects and arachnids),and helminths (including nematodes).

In the following preferred definitions it is generally to be understoodthat where symbols are not specifically defined they are to be aspreviously defined in the description.

Preferably R¹ is CN, CSNH₂ or C(═N—Z)—S(O)₁-Q; wherein Z is H,(C₁-C₃)-alkyl, —(CH₂)_(q)R⁷, COR⁸, CO₂—(C₁-C₃)-alkyl or S(O)_(p)R⁸, inwhich R⁷ is phenyl unsubstituted or substituted by one or more radicalsselected from the group consisting of halogen, (C₁-C₃)-alkyl,(C₁-C₃)-haloalkyl, (C₁-C₃)-alkoxy, CN and NO₂, and each R⁸ is(C₁-C₃)-alkyl or (C₁-C₃)-haloalkyl; Q is (C₁-C₃)-alkyl and r is zero.

More preferably R¹ is CN or CSNH₂.

Preferably W is C—Cl or N (more preferably W is C—Cl).

Preferably R² is Cl.

Preferably R³ is CF₃ or OCF₃ (more preferably R³ is CF₃).

Preferably R⁴ is hydrogen, (C₂-C₄)-alkenyl, (C₂-C₄)-haloalkenyl,(C₂-C₄)-alkynyl, (C₂-C₄)-haloalkynyl, (C₃-C₇)-cycloalkyl,CO₂—(C₁-C₄)-alkyl, CO₂—(C₃-C₄)-alkynyl, CO₂—(C₃-C₄)-alkynyl,CO2—(CH₂)_(m)R⁷ or SO₂R⁸; or (C₁-C₄)-alkyl unsubstituted or substitutedby one or more radicals selected from the group consisting of halogen,(C₁-C₃)-alkoxy, (C₁-C₄)-haloalkoxy, (C₃-C₇)-cycloalkyl and S(O)_(p)R⁸;wherein R⁷ is phenyl unsubstituted or substituted by one or moreradicals selected from the group consisting of halogen, (C₁-C₃)-alkyl,(C₁-C₃)-haloalkyl, (C₁-C₃)-alkoxy, (C₁-C₃)-haloalkoxy, CN, NO₂ andS(O)_(p)R⁸; and each R⁸ is (C₁-C₃)-alkyl or (C₁-C₃)-haloalkyl. Morepreferably R⁴ is CO₂—(C₁-C₃)-alkyl or SO₂R⁸; or (C₁-C₃)-alkylunsubstituted or substituted by one or more radicals selected from thegroup consisting of halogen, (C₁-C₃)-alkoxy, S(O)_(p)R⁸ andCO₂—(C₁-C₃)-alkyl, wherein R⁸ is (C₁-C₃)-alkyl or (C₁-C₃)-haloalkyl.Most preferably R⁴ is (C₁-C₃)-alkyl.

Preferably A is (C₁-C₄)-alkylene.

More preferably A is —CH₂CH₂— or —CH₂CH₂CH₂—.

Preferably R⁵ is (C₃-C₄)-alkenyl, (C₃-C₄)-alkynyl, (C₃-C₇)-cycloalkyl or—CH₂)_(q)R⁷; or (C₁-C₄)-alkyl unsubstituted or substituted by one ormore radicals selected from the group consisting of halogen,(C₁-C₄)-alkoxy, (C₁-C₄)-haloalkoxy, (C₃-C₄)-alkenyloxy,(C₃-C₄)-haloalkenyloxy, (C₃-C₄)-alkynyloxy, (C₃-C₄)-haloalkynyloxy,(C₃-C₇)-cycloalkyl, S(O)_(p)R⁸, CN, NO₂, OH, COR⁹ and CO₂R⁹, wherein R⁷is phenyl unsubstituted or substituted by one or more radicals selectedfrom the group consisting of halogen, (C₁-C₃)-alkyl, (C₁-C₃)-haloalkyl,(C₁-C₃)-alkoxy, (C₁-C₃)-haloalkoxy, CN, NO₂ and S(O)_(p)R⁸; each R⁸ is(C₁-C₃)-alkyl or (C₁-C₃)-haloalkyl; and R⁹ is H or (C₁-C₃)-alkyl.

More preferably R⁵ is (C₃-C₄)-alkenyl, (C₃-C₄)-alkynyl, —CH₂)_(q)R⁷,(C₁-C₃)-alkyl or (C₁-C₃)-haloalkyl, wherein R⁷ is phenyl unsubstitutedor substituted by one or more radicals selected from the groupconsisting of halogen, (C₁-C₃)-alkyl, (C₁-C₃)-haloalkyl, (C₁-C₃)-alkoxy,(C₁-C₃)-haloalkoxy, CN, NO₂ and S(O)_(p)R⁸; and each R⁸ is (C₁-C₃)-alkylor (C₁-C₃)-haloalkyl.

Preferably R⁶ is (C₁-C₃)-haloalkyl (more preferably R⁶ is CF₃).

A preferred class of compounds of formula (I) for use in the inventionare those in which:

-   R¹ is CN, CSNH₂ or C(═N—Z)—S-Q (more preferably R¹ is CN or CSNH₂);-   Z is H, (C₁-C₃)-alkyl, —(CH₂)_(q)R⁷, COR⁸, CO₂—(C₁-C₃)-alkyl or    S(O)_(p)R⁸;-   Q is (C₁-C₃)-alkyl;-   W is C—Cl or N;-   R² is Cl;-   R³ is CF₃ or OCF₃ (more preferably R³ is CF₃);-   R⁴ is hydrogen, (C₂-C₄)-alkenyl, (C₂-C₄)-haloalkenyl,    (C₂-C₄)-alkynyl, (C₂-C₄)-haloalkynyl, (C₃-C₇)-cycloalkyl,    CO₂—(C₁-C₄)-alkyl, CO₂—(C₃-C₄)-alkenyl, CO₂—(C₃-C₄)-alkynyl,    CO₂—(CH₂)_(m)R⁷ or SO₂R⁸; or (C₁-C₄)-alkyl unsubstituted or    substituted by one or more radicals selected from the group    consisting of halogen, (C₁-C₃)-alkoxy, (C₁-C₃)-haloalkoxy,    (C₃-C₇)-cycloalkyl and S(O)_(p)R⁸ (more preferably R⁴ is    CO₂—(C₁-C₃)-alkyl or SO₂R⁸; or (C₁-C₃)-alkyl unsubstituted or    substituted by one or more radicals selected from the group    consisting of halogen, (C₁-C₃)-alkoxy, S(O)_(p)R⁸ and    CO₂—(C₁-C₃)-alkyl);-   A is (C₁-C₄)-alkylene (more preferably A is —CH₂CH₂— or    —CH₂CH₂CH₂—);-   X is C(═O), C(═S) or SO₂;-   Y is O, NH or a covalent bond;-   R⁵ is (C₃-C₄)-alkenyl, (C₃-C₄)-alkynyl, (C₃-C₇)-cycloalkyl or-   (CH₂)_(q)R⁷; or (C₁-C₄-alkyl unsubstituted or substituted by one or    more radicals selected from the group consisting of halogen,    (C₁-C₄)-alkoxy, (C₁-C₄)-haloalkoxy, (C₃-C₄)-alkenyloxy,    (C₃-C₄)-haloalkenyloxy, (C₃-C₄)-alkynyloxy, (C₃-C₄)-haloalkynyloxy,    (C₃-C₇)-cycloalkyl, S(O)_(p)R⁸, CN, NO₂, OH, COR⁹ and CO₂R⁹ (more    preferably R⁵ is (C₃-C₄)-alkenyl, (C₃-C₄)-alkynyl, —(CH₂)_(q)R⁷,    (C₁-C₃)-alkoxy, (C₁-C₃)-alkyl or (C₁-C₃)-haloalkyl);-   R⁶ is (C₁-C₃)-haloalkyl (more preferably R⁶ is CF₃);-   each R⁷ is independently phenyl unsubstituted or substituted by one    or more radicals selected from the group consisting of halogen,    (C₁-C₃)-alkyl, (C₁-C₃)-haloalkyl, (C₁-C₃)-alkoxy,    (C₁-C₃)-haloalkoxy, CN, NO₂ and S(O)_(p)R⁸;-   each R⁸ is independently (C₁-C₃)-alkyl or (C₁-C₃)-haloalkyl; and-   R⁹ is H or (C₁-C₃)-alkyl.

A further preferred class of compounds of formula (I) are those wherein:

-   R¹ is CN, CSNH₂ or C(═N—Z)—S-Q;-   Z is H, (C₁-C₃)-alkyl, —(CH₂)_(q)R⁷, COR⁸, CO₂—(C₁-C₃)-alkyl or    S(O)_(p)R⁸;-   Q is (C₁-C₃)-alkyl;-   W is C—Cl;-   R² is Cl;-   R³ is CF₃;-   R⁴ is hydrogen, (C₂-C₄)-alkenyl, (C₂-C₄)-alkynyl,    (C₃-C₇)-cycloalkyl, CO₂—(C₁-C₄)-alkyl, CO₂—(C₃-C₄)-alkenyl,    CO₂—(C₃-C₄)-alkynyl, CO₂—(CH₂)_(m)R⁷ or SO₂R⁸; or (C₁-C₃)-alkyl    unsubstituted or substituted by one or more radicals selected from    the group consisting of halogen, (C₁-C₃)-alkoxy, S(O)_(p)R⁸ and    CO₂—(C₁-C₃)-alkyl);-   A is —CH₂CH₂— or —CH₂CH₂CH₂—;-   X is C(═O) or SO₂;-   Y is O, NH or a covalent bond;-   R⁵ is (C₃-C₄)-alkenyl, (C₃-C₄)-alkynyl, —(CH₂)_(q)R⁷, (C₁-C₃)-alkyl    or (C₁-C₃)-haloalkyl;-   R⁶ is CF₃;-   each R⁷ is independently phenyl unsubstituted or substituted by one    or more radicals selected from the group consisting of halogen,    (C₁-C₃)-alkyl, (C₁-C₃)-haloalkyl, (C₁-C₃)-alkoxy,    (C₁-C₃)-haloalkoxy, CN, NO₂ and S(O)_(p)R⁸; and-   each R⁸ is independently (C₁-C₃)-alkyl or (C₁-C₃)-haloalkyl.

A further preferred class of compounds of formula (I) are those wherein:

-   R¹ is CN or CSNH₂;-   W is C—Cl;-   R² is Cl;-   R³ is CF₃;-   R⁴ is (C₁-C₃)-alkyl;-   A is —CH₂CH₂— or —CH₂CH₂CH₂—;-   X is C(═O);-   Y is O, NH or a covalent bond;-   R⁵ is (C₃-C₄)-alkenyl, (C₃-C₄)-alkynyl, —(CH₂)_(q)R⁷, (C₁-C₃)-alkyl    or (C₁-C₃)-haloalkyl;-   R⁶ is CF₃;-   R⁷ is phenyl unsubstituted or substituted by one or more radicals    selected from the group consisting of halogen, (C₁-C₃)-alkyl,    (C₁-C₃)-haloalkyl, (C₁-C₃)-alkoxy, (C₁-C₃)-haloalkoxy, CN, NO₂ and    S(O)_(p)R⁸; and-   R⁸ is (C₁-C₃)-alkyl or (C₁-C₃)-haloalkyl.

A further preferred class of compounds of formula (I) are those wherein:

-   R¹ is CN;-   W is C—Cl;-   R² is Cl;-   R³ is CF₃;-   R⁴ is methyl;-   A is —CH₂CH₂—;-   X is C(═O) or SO₂;-   Y is O, NH or a covalent bond;-   R⁵ is (C₃-C₄)-alkenyl, (C₃-C₆)-cycloalkyl or —CH₂)_(q)R⁷; or    (C₁-C₃)-alkyl unsubstituted or substituted by one or more radicals    selected from the group consisting of halogen and (C₁-C₆)-alkoxy;-   R⁶ is CF₃; and-   R⁷ is phenyl unsubstituted or substituted by one or more radicals    selected from the group consisting of halogen, (C₁-C₃)-alkyl,    (C₁-C₃)-haloalkyl, (C₁-C₃)-alkoxy, (C₁-C₃)-haloalkoxy and NO₂.

The compounds of general formula (I) can be prepared by the applicationor adaptation of known methods (i.e. methods heretofore used ordescribed in the chemical literature.

In the following description of processes when symbols appearing informulae are not specifically defined, it is understood that they are“as defined above” in accordance with the first definition of eachsymbol in the specification.

According to a feature of the invention compounds of formula (I) whereinR², R³, R⁴, R⁵, R⁶, W, A and n are as defined above, R¹ is CN, and Y andX are as defined above with the exclusion of compounds in which —Y—X— is—NH—CO— or —NH—CS—, may be prepared by the acylation or sulfonylation ofa compound of formula (II):

wherein R², R³, R⁴, R⁶, W, A and n are as defined above, with a compoundof formula (III):R⁵—Y—X-L  (III)wherein Y and X are as defined above with the exclusion of compounds inwhich —Y—X— is —NH—CO— or —NH—CS—, and L is a leaving group. Foracylations, where X is CO or CS, and Y is O or a covalent bond, (III) ispreferably an acid halide and L is preferably chlorine or bromine (morepreferably chlorine). A base is optionally present in the reaction whichis generally performed in an inert solvent such as tetrahydrofuran,dioxan, acetonitrile, toluene, diethyl ether, dichloromethane,dimethylsulfoxide or N,N-dimethylformamide, at a temperature of from 0°C. to 150° C., preferably at 20° C. to 100° C. The base is generally analkali metal hydroxide such as potassium hydroxide, an alkali metalhydride such as sodium hydride, an alkali metal carbonate such aspotassium carbonate or sodium carbonate, an alkali metal alkoxide suchas sodium methoxide, an alkaline earth metal carbonate such as calciumcarbonate, or an organic base such as a tertiary amine, for exampletriethylamine or ethyldiisopropylamine, or pyridine, or1,8-diazabicyclo[5.4.0]undec-7-en (DBU).

For sulfonylations, where X is SO₂, (III) is preferably a sulfonylhalide and L is preferably chlorine or bromine (more preferablychlorine). A base is optionally present in the reaction, which isgenerally performed using similar bases, solvents and temperatures asemployed for the acylation reactions.

According to a further feature of the invention compounds of formula (I)wherein R¹ is CN, —Y—X— is —NH—CO— or —NH—CS—, and R², R³, R⁴, R⁵, R⁶,W, A and n are as defined above, may be prepared by the reaction of acompound of formula (II), wherein R¹, R², R³, R⁶, W, A and n are asdefined above, with an isocyanate or isothiocyanate compound of formula(IV) or (V):R⁵—N═C═O  (IV)R⁵—N═C═S  (V)wherein R⁵is as defined above. The reaction is optionally performed inthe presence of a base, such as an alkali metal hydride for examplesodium hydride, in an inert solvent such as acetonitrile ortetrahydrofuran, at a temperature of from 0° to 100° C.

According to a further feature of the invention compounds of formula (I)wherein R¹ is CN, n is 1 or 2, and R², R³, R⁴, R⁵, R⁶, W, A, X and Y areas defined above, may be prepared by oxidising a corresponding compoundin which n is 0 or 1. The oxidation is generally performed using aperacid such as 3-chloroperbenzoic acid in a solvent such asdichloromethane or 1,2-dichloroethane, at a temperature of from 0° C. tothe reflux temperature of the solvent.

According to a further feature of the invention compounds of formula (I)wherein R¹ is CSNH₂, and R², R³, R⁴, R⁵, R⁶, W, A, X, Y and n are asdefined above, may be prepared by the reaction of the correspondingcompound of formula (I) wherein R¹ is CN, with an alkali or alkalineearth metal hydrosulfide, such as lithium, potassium, calcium orpreferably sodium hydrosulfide, in an inert solvent for exampleN,N-dimethylformamide, pyridine, dioxan, tetrahydrofuran, sulfolane,dimethyl sulfoxide, methanol or ethanol at a temperature from −35° C. to50° C. preferably 0° C. to 30° C. Optionally the hydrosulfide may begenerated in situ by treatment with H₂S in the presence of an organicbase, such as a metal alkoxide or trialkylamine or an inorganic base,such as an alkaline or alkaline earth metal hydroxide or a carbonate,such as sodium, potassium or ammonium carbonate. The use of a metalcomplexing agent, such as a crown ether, can be of benefit inaccelerating the reaction. The reaction of hydrosulfide salt with thecompound of formula (II) can also be conducted in a two-phasewater/organic solvent system using a phase transfer catalyst such as acrown ether or a tetraalkylammonium salt such as tetra-n-butylammoniumbromide or benzyltrimethylammonium chloride. Organic solvents suitablefor use in a two-phase system with water include benzene, toluene,dichloromethane, 1-chlorobutane and methyl tertiary-butyl ether.Alternatively compounds of formula (I) wherein R¹ is CSNH₂, may also beprepared from the corresponding compound of formula (I) wherein R¹ isCN, by treatment with the reagent Ph₂PS₂, as described in Tet. Lett., 24(20), 2059 (1983).

According to a further feature of the invention compounds of formula (I)wherein R¹ is CSNH₂, and R², R³, R⁴, R⁵, R⁶, W, A, X, Y and n are asdefined above, may be prepared by the reaction of the correspondingcompound of formula (I) wherein R¹ is CN, with abis(trialkylsilyl)sulfide, preferably bis(trimethylsilyl)sulfide, in thepresence of a base generally an alkali metal alkoxide such as sodiummethoxide, in a solvent such as N,N-dimethylforrnamide, at a temperatureof from 0° C. to 60° C. The procedure is generally described by Lin, Kuand Shiao in Synthesis 1219 (1992).

According to a further feature of the invention compounds of formula (I)wherein R¹ is C(═N—H)—S-Q, and Q, R², R³, R⁴, R⁵, R⁶, W, A, X, Y and nare as defined above, may be prepared by the reaction of thecorresponding compound of formula (I) wherein R¹ is CSNH₂ with analkylating agent of formula (VI) or (VII):Q-L¹  (VI)Q₃O⁺BF₄ ⁻  (VII)wherein Q is as defined above and L¹ is a leaving group, generallyhalogen and preferably chlorine, bromine or iodine. The reaction isgenerally performed in the presence of a base, for example an alkalimetal hydride such as sodium hydride, or an alkali metal alkoxide suchas potassium tert-butoxide, in an inert solvent such as tetrahydrofuranat a temperature from 0 to 60° C. Alternatively an alkali metalcarbonate such as potassium carbonate, or an organic base such as atrialkylamine, for example triethylamine or N,N-diisopropylethylaminemay be used, in an inert solvent such as acetone, at a temperature from0° C. to the reflux temperature of the solvent. When a compound offormula (VII) such as trimethyloxonium tetrafluoroborate is used as thealkylating agent, the base is preferably an alkali metal bicarbonatesuch as sodium bicarbonate, the solvent is for example dichloromethane,and the temperature is from 0° C. to the reflux temperature of thesolvent.

According to a further feature of the present invention compounds offormula (I) wherein R¹ is C(═N-Z)-S-Q, Z is as defined above with theexclusion of H, and the other values are as defined in formula (I), maybe prepared by the alkylation, acylation or sulfonylation of thecorresponding compound of formula (I) wherein Z is H, with a compound offormula (VIII):Z-L²  (VIII)wherein Z is as defined above with the exclusion of H, and L² is aleaving group. For alkylations, where Z is (C₁-C₆)-alkyl,(C₁-C₆)-haloalkyl, (C₃-C₆)-alkenyl, (C₃-C₆)-alkynyl or —(CH₂)_(q)R⁷, L²is preferably halogen, alkylsulfonyloxy or arylsulfonyloxy (morepreferably chlorine, bromine, iodine, methylsulfonyloxy orp-toluenesulfonyloxy). A base is optionally present in the reactionwhich is generally performed in an inert solvent such astetrahydrofuran, dioxan, acetonitrile, toluene, diethyl ether,dichloromethane, dimethylsulfoxide or N,N-dimethylformamide, at atemperature of from −30° C. to 200° C., preferably at 20° C. to 100° C.The base is generally an alkali metal hydroxide such as potassiumhydroxide, an alkali metal hydride such as sodium hydride, an alkalimetal carbonate such as potassium carbonate or sodium carbonate, analkali metal alkoxide such as sodium methoxide, an alkaline earth metalcarbonate such as calcium carbonate, or an organic base such as atertiary amine, for example triethylamine or ethyidiisopropylamine, orpyridine, or 1,8-diazabicyclo[5.4.0]undec-7-en (DBU). For acylations,where Z is COR⁸ or CO₂—(C₁-C₆)-alkyl, (VIII) is preferably an acidhalide where L² is preferably chlorine or bromine (more preferablychlorine). A base is optionally present in the reaction, which isgenerally performed using similar bases, solvents and temperatures asemployed for the alkylations. For sulfonylations, where Z is S(O)_(p)R⁸,(VIII) is preferably a sulfonyl halide where L² is preferably chlorineor bromine (more preferably chlorine). A base is optionally present inthe reaction, which is generally performed using similar bases, solventsand temperatures as employed for the alkylations.

Intermediates of formula (II) wherein A is —CH₂CH₂—, and R², R³, R⁴, R⁶,W and n are as defined above, may conveniently be prepared by thereaction of a compound of formula (IX):

with ethylene oxide. The reaction is generally carried out in thepresence of a catalyst, which may be a base or an acid, in an inertsolvent at a temperature of from 0° C. to the reflux temperature.

Intermediates of formula (II) wherein A is —CH₂CH₂—, R², R³, R⁶, W and nare as defined above, and R⁴ is as defined above with the exclusion ofH, may be prepared by the alkylation, acylation or sulfonylation of thecorresponding compound of formula (II) in which R⁴ is H, according toknown conditions. In certain cases it may be necessary to employsuitable protecting groups in order to avoid reaction at the hydroxygroup, with subsequent removal of the protecting group after theintroduction of the appropriate R⁴ moiety. Suitable methods ofprotection are well known in the art.

Intermediates of formula (II) wherein n is 2, and R², R³, R⁴, R⁶, W andA are as defined above, may be prepared by the reaction of a compound offormula (X):

wherein R², R³, R⁴, R⁶, W and A are as defined above, n is 2 and L³ is aleaving group, generally halogen and preferably bromine, with a compoundof formula (XI):HO-A-NHR⁴  (XI)wherein R⁴ is as defined above. The reaction is performed in thepresence of a base, in an inert solvent such as tetrahydrofuran, dioxan,acetonitrile, toluene, diethyl ether, dichloromethane, dimethylsulfoxideor N,N-dimethylformamide, at a temperature of from 0° C. to 100° C. Thebase is generally an alkali metal hydride such as sodium hydride, analkali metal carbonate such as potassium carbonate or sodium carbonate,an alkali metal alkoxide such as sodium methoxide, or an alkaline earthmetal carbonate such as calcium carbonate.

Intermediates of formula (II) wherein R², R³, R⁴, R⁶, W, A and n are asdefined above, may in addition be prepared according to other knownmethods.

Collections of compounds of the formula (I) which can be synthesized bythe above mentioned process may also be prepared in a parallel manner,and this may be effected manually or in a semiautomated or fullyautomated manner. In this case, it is possible, for example, to automatethe procedure of the reaction, work-up or purification of the productsor of the intermediates. In total, this is to be understood as meaning aprocedure as is described, for example, by S. H. DeWitt in “AnnualReports in Combinatorial Chemistry and Molecular Diversity: AutomatedSynthesis”, Volume 1, Verlag Escom 1997, pages 69 to 77.

A series of commercially available apparatuses as are offered by, forexample, Stem Corporation, Woodrolfe Road, Tollesbury, Essex, CM9 8SE,England or H+P Labortechnik GmbH, Bruckmannring 28, 85764Oberschleiβheim, Germany or Radleys, Shirehill, Saffron Walden, Essex,England, may be used for the parallel procedure of the reaction andwork-up. For the parallel purification of compounds of the formula (I),or of intermediates obtained during the preparation, use may be made,inter alia, of chromatography apparatuses, for example those by ISCO,Inc., 4700 Superior Street, Lincoln, Nebr. 68504, USA.

The apparatuses mentioned lead to a modular procedure in which theindividual process steps are automated, but manual operations must beperformed between the process steps. This can be prevented by employingsemi-integrated or fully integrated automation systems where theautomation modules in question are operated by, for example, robots.Such automation systems can be obtained, for example, from ZymarkCorporation, Zymark Center, Hopkinton, Mass. 01748, USA.

In addition to what has been described here, compounds of the formula(I) may be prepared in part or fully by solid-phase-supported methods.For this purpose, individual intermediate steps or all intermediatesteps of the synthesis or of a synthesis adapted to suit the procedurein question are bound to a synthetic resin. Solid-phase-supportedsynthesis methods are described extensively in the specialistliterature, for example Barry A. Bunin in “The Combinatorial Index”,Academic Press, 1998.

The use of solid-phase-supported synthesis methods permits a series ofprotocols which are known from the literature and which, in turn, can beperformed manually or in an automated manner. For example, the “tea-bagmethod” (Houghten, U.S. Pat. No. 4,631,211; Houghten et al., Proc. Natl.Acad. Sci, 1985, 82, 5131-5135), in which products by IRORI, 11149 NorthTorrey Pines Road, La Jolla, Calif. 92037, USA, are employed, may besemiautomated. The automation of solid-phase-supported parallelsyntheses is performed successfully, for example, by apparatuses byArgonaut Technologies, Inc., 887 Industrial Road, San Carlos, Calif.94070, USA or MultiSynTech GmbH, Wullener Feld 4, 58454 Witten, Germany.

The preparation of the processes described herein yields compounds ofthe formula (I) in the form of substance collections which are termedlibraries. The present invention also relates to libraries whichcomprise at least two compounds of the formula (I).

Compounds of formula (III), (IV), (V), (VI), (VII), (VIII), (IX), (X)and (XI) are known or may be prepared by known methods.

The following non-limiting Examples illustrate the preparation of thecompounds of formula (I).

CHEMICAL EXAMPLES

NMR spectra were run in deuterochloroform unless stated otherwise.

In the Examples which follow, quantities (also percentages) are weightbased, unless stated otherwise. Ratios of solvents are volume based.

Example 11-(2,6-Dichloro-4-trifluoromethylphenyl)-3-cyano-5-{N-methyl-N-[2-(4-toluenesulfonyloxy)ethyl]amino}-4-trifluoromethylsulfonylpyrazole

A solution of1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-5-[N-(2-hydroxyethyl)-N-methylamino]-4-trifluoromethylsulfonylpyrazole(0.100 g, 0.2 mmol) and sodium hydride (0.016 g, 0.4 mmol) in drytetrahydrofuran was stirred vigorously under an atmosphere of nitrogenfor 1 hour at 20° C. 4-Toluenesulfonyl chloride (0.056 g, 0.3 mmol) wasthen added and stirring continued for 1 hour at 20° C. The mixture wasthen added to saturated ammonium chloride solution and ethyl acetate;and the organic layer washed with water and brine, dried (sodiumsulfate) and evaporated. The residue was purified by flash columnchromatography eluting with heptane/ethyl acetate (4:1) to afford thetitle compound as a fine white powder (0.074 g, Compound 93, yield 55%),19F-NMR: −64.2, −79.2.

Example 21-(2,6-Dichloro-4-trifluoromethylphenyl)-3-cyano-5-{N-methyl-N-[2-(4-trifluoromethyl-benzoyloxy)ethyl]amino}-4-trifluoromethylsulphonylpyrazole

Sodium hydride (0.012 g, 0.3 mmol) was added to a solution of1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-5-[N-(2-hydroxyethyl)-N-methylamino]-4-trifluoromethylsulfonylpyrazole(0.100 g, 0.2 mmol) in dry tetrahydrofuran, and the mixture vigorouslystirred under a nitrogen atmosphere for 1 hour at 20° C.4-Trifluoromethylbenzoyl chloride (0.053 g, 0.3 mmol) was added and theresulting mixture stirred for 2 hours at 20° C. The mixture was pouredinto saturated ammonium chloride solution and ethyl acetate, and theorganic layer washed with water and brine, dried (sodium sulfate) andevaporated. The residue was purified by flash column chromatographyeluting with heptane/ethyl acetate (4:1) to give the title compound as apale oil (0.085 g, Compound 54, yield 61%), 19F-NMR: −63.7, −63.8,−78.6.

Example 31-(2,6-Dichloro-4-trifluoromethylphenyl)-3-cyano-5-{N-methyl-N-[2-(4-ethoxyphenylaminocarbonyloxy)ethyl]amino)}-4-trifluoromethylsulfonylpyrazole

Sodium hydride (0.012 g, 0.3 mmol) was added to a solution of1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-5-[N-(2-hydroxyethyl)-N-methylamino]-4-trifluoromethylsulfonylpyrazole(0.100 g, 0.2 mmol) in dry tetrahydrofuran, and stirred vigorously undera nitrogen atmosphere for 1 hour at 20° C. 4-Ethoxyphenylisocyanate(0.041 g, 0.3 mmol) was added and stirring continued for 2 hours at 20°C. The mixture was poured into saturated ammonium chloride solution andethyl acetate and the organic layer washed with water and brine, dried(sodium sulfate), and evaporated. The residue was purified via flashcolumn chromatography eluting with heptane/ethyl acetate (4:1 to 2:1) togive the title compound as a white powder (0.041 g, Compound 69, yield30%), 19F-NMR: −63.7, −78.5.

Example 41-(2,6-Dichloro-4-trifluoromethylphenyl)-3-cyano-5-{N-methyl-N-[2-(ethoxycarbonyloxy)ethyl]amino}-4-trifluoromethylsulfonylpyrazole

Sodium hydride (0.012 g, 0.3 mmol) was added to a solution of1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-5-[N-(2-hydroxyethyl)-N-methylamino]-4-trifluoromethylsulfonylpyrazole(0.100 g, 0.2 mmol) in dry tetrahydrofuran, and stirred under anatmosphere of nitrogen for 2 hours at 20° C. Ethyl chloroformate (0.029g, 0.3 mmol) was added and stirring continued for 1 hour at 20° C. Themixture was then added to saturated ammonium chloride solution and ethylacetate, and the organic layer washed with water and brine, dried(sodium sulfate), and evaporated. The residue was purified by flashcolumn chromatography eluting with heptane/ethyl acetate (4:1) to givethe title compound as a white powder (0.098 g, Compound 6, yield: 81%),19F-NMR: −63.8, −78.6.

The following Intermediate Examples illustrate the preparation ofintermediates used in the synthesis of the above Examples.

Intermediate Example 1

Finely powdered potassium carbonate (7.29 g, 52.2 mmol) was added to asolution of5-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulphonylpyrazole(10.00 g, 19.3 mmol) in dry N,N-dimethylformamide (85 ml) and stirredfor 1 hour at 20° C. 2-(Methylamino)ethanol (3.11 ml, 38.7 mmol) wasthen added and stirring continued for 2 hours at 20° C. The resultingmixture was poured into saturated ammonium chloride solution, extractedwith ethyl acetate, and the organic layer washed with water and brine,dried (sodium sulfate), evaporated and purified by column chromatographyeluting with hexane and ethyl acetate (2:1) to give1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-5-[N-(2-hydroxyethyl)-N-methylamino]-4-trifluoromethylsulfonylpyrazoleas a fine white powder (5.65 g, yield 57%), 19F-NMR: −63.7, −78.4.

Intermediate Example 2

t-Butyinitrite (84 ml, 0.662 mol) was added to a suspension of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulfonylpyrazole(100 g, 0.221 mol) in bromoform (320 ml). The resulting mixture washeated to 60-70° C. for 3 hours. Another portion of t-butylnitrite (84ml, 0.662 mol) was added and the mixture stirred at 60-70° C. for afurther 2.5 hours. It was then cooled, washed with hexane,hexane-toluene, and then filtered. The solid was washed with pentane andvacuum dried to give5-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulfonylpyrazoleas a yellow solid (96.69 g, 79% yield), mp 142° C.

The following preferred compounds shown in Table 1 also form part of thepresent invention, and were or may be prepared in accordance with, oranalogously to, the above-mentioned Examples 1 to 4 or theabove-described general methods. In the Tables Me means methyl, Et meansethyl, Pr means n-propyl, i-Pr means isopropyl, cPr means cyclopropyl,OMe means methoxy, OEt means ethoxy, Ph means phenyl and CH₂(2-F Ph)means 2-fluorobenzyl.

19F-NMR spectra shift values are given in ppm.

Compound numbers are given for reference purposes only.

TABLE I Compounds of formula (I) in which the substituents have thefollowing meanings: R¹ = CN, R⁴ is Me, R⁶ is CF₃, A is —CH₂CH₂—, W =C—Cl, R² = Cl, R³ = CF₃. Cpd No. X Y R⁵ n mp ° C. 19F-NMR 1 CO O Me 0 2CO O Me 1 3 CO O Me 2 4 CO O Et 0 5 CO O Et 1 6 CO O Et 2 −63.8, −78.6 7CO O Pr 0 8 CO O Pr 1 9 CO O Pr 2 10 CO O iPr 0 11 CO O iPr 1 12 CO OiPr 2 −63.7, −78.5 13 CO O CH₂CH═CH₂ 0 14 CO O CH₂CH═CH₂ 1 15 CO OCH₂CH═CH₂ 2 16 CO O cPr 0 17 CO O cPr 1 18 CO O cPr 2 19 CO O Ph 0 20 COO Ph 1 21 CO O Ph 2 22 CO O 4-CF₃Ph 0 23 CO O 4-CF₃Ph 1 24 CO O 4-CF₃Ph2 25 CO O 4-MePh 0 26 CO O 4-MePh 1 27 CO O 4-MePh 2 28 CO O 4-NO₂Ph 029 CO O 4-NO₂Ph 1 30 CO O 4-NO₂Ph 2 −64.2, −79.0 31 CO O 4-OMePh 0 32 COO 4-OMePh 1 33 CO O 4-OMePh 2 34 CO O 4-OEtPh 0 35 CO O 4-OEtPh 1 36 COO 4-OEtPh 2 37 CO covalent bond Me 0 38 CO covalent bond Me 1 39 COcovalent bond Me 2 −63.8, −78.6 40 CO covalent bond Et 0 41 CO covalentbond Et 1 42 CO covalent bond Et 2 43 CO covalent bond Et 0 44 COcovalent bond Et 1 45 CO covalent bond Et 2 46 CO covalent bond Pr 0 47CO covalent bond Pr 1 48 CO covalent bond Pr 2 49 CO covalent bondCH₂OMe 0 50 CO covalent bond CH₂OMe 1 51 CO covalent bond CH₂OMe 2−64.2, −79.1 52 CO covalent bond 4-CF₃Ph 0 53 CO covalent bond 4-CF₃Ph 154 CO covalent bond 4-CF₃Ph 2 −63.7, −63.8, −78.6 55 CO covalent bone2,6-F₂Ph 0 56 CO covalent bond 2,6-F₂Ph 1 57 CO covalent bond 2,6-F₂Ph 2−63.7, −78.7, −110.2 58 CO covalent bond Ph 0 59 CO covalent bond Ph 160 CO covalent bond Ph 2 61 CO covalent bond 2-FPh 0 62 CO covalent bond2-FPh 1 63 CO covalent bond 2-FPh 2 −63.8, −78.7 64 CO NH 4-MeOPh 0 65CO NH 4-MeOPh 1 66 CO NH 4-MeOPh 2 67 CO NH 4-EtOPh 0 68 CO NH 4-EtOPh 169 CO NH 4-EtOPh 2 −63.7, −78.5 70 CO NH 4-CF₃OPh 0 71 CO NH 4-CF₃OPh 172 CO NH 4-CF₃OPh 2 −58.7, −63.7, −78.5, −78.9 73 CO NH 4-CF₃Ph 0 74 CONH 4-CF₃Ph 1 75 CO NH 4-CF₃Ph 2 76 SO₂ covalent bond Me 0 77 SO₂covalent bond Me 1 78 SO₂ covalent bond Me 2 −63.8, −78.6 79 SO₂covalent bond Et 0 80 SO₂ covalent bond Et 1 81 SO₂ covalent bond Et 282 SO₂ covalent bond Pr 0 83 SO₂ covalent bond Pr 1 84 SO₂ covalent bonePr 2 −64.3, −79.1 85 SO₂ covalent bond CH₂Ph 0 86 SO₂ covalent bondCH₂Ph 1 87 SO₂ covalent bond CH₂Ph 2 −64.2, −79.1 88 SO₂ covalent bone4-ClPh 0 89 SO₂ covalent bond 4-ClPh 1 90 SO₂ covalent bond 4-ClPh 2−64.2, −79.2 91 SO₂ covalent bond 4-MePh 0 92 SO₂ covalent bond 4-MePh 193 SO₂ covalent bond 4-MePh 2 −64.2, −79.2 94 SO₂ covalent bondCH₂(2-FPh) 0 95 SO₂ covalent bond CH₂(2-FPh) 1 96 SO₂ covalent bondCH₂(2-FPh) 2 97 SO₂ covalent bond CH₂(4-ClPh) 2 98 SO₂ covalent bondCH₂(4-MePh) 0 99 SO₂ covalent bond CH₂(4-MePh) 1 100 SO₂ covalent bondCH₂(4-MePh) 2 101 SO₂ covalent bond CH₂(4-ClPh) 0 102 SO₂ covalent bondCH₂(4-ClPh) 1 103 SO₂ covalent bond CH₂(4-ClPh) 2

According to a further feature of the present invention there isprovided a method for the control of pests at a locus which comprisesapplying thereto an effective amount of a compound of formula (I) or asalt thereof. For this purpose, the said compound is norrnally used inthe form of a pesticidal composition (i.e. in association withcompatible diluents or carriers and/or surface active agents suitablefor use in pesticidal compositions), for example as hereinafterdescribed.

The term “compound of the invention” as used hereinafter embraces a5-substituted-oxyalkylaminopyrazole of formula (I) as defined above anda pesticidally acceptable salt thereof.

One aspect of the present invention as defined above is a method for thecontrol of pests at a locus. The locus includes, for example, the pestitself, the place (plant, field, forest, orchard, waterway, soil, plantproduct, or the like) where the pest resides or feeds, or a placesusceptible to future infestation by the pest. The compound of theinvention may therefore be applied directly to the pest, to the placewhere the pest resides or feeds, or to the place susceptible to futureinfestation by the pest.

As is evident from the foregoing pesticidal uses, the present inventionprovides pesticidally active compounds and methods of use of saidcompounds for the control of a number of pest species which includes:arthropods, especially insects or mites, or plant nematodes. Thecompound of the invention may thus be advantageously employed inpractical uses, for example, in agricultural or horticultural crops, inforestry, in veterinary medicine or livestock husbandry, or in publichealth.

The compounds of the invention may be used for example in the followingapplications and on the following pests:

For the control of soil insects, such as corn rootworm, termites(especially for protection of structures), root maggots, wireworms, rootweevils, stalkborers, cutworms, root aphids, or grubs. They may also beused to provide activity against plant pathogenic nematodes, such asroot-knot, cyst, dagger, lesion, or stem or bulb nematodes, or againstmites. For the control of soil pests, for example corn rootworm, thecompounds are advantageously applied to or incorporated at an effectiverate into the soil in which crops are planted or to be planted or to theseeds or growing plant roots.

In the area of public health, the compounds are especially useful in thecontrol of many insects, especially filth flies or other Dipteran pests,such as houseflies, stableflies, soldierflies, homflies, deerflies,horseflies, midges, punkies, blackflies, or mosquitoes.

In the protection of stored products, for example cereals, includinggrain or flour, groundnuts, animal feedstuffs, timber or householdgoods, e.g. carpets and textiles, compounds of the invention are usefulagainst attack by arthropods, more especially beetles, includingweevils, moths or mites, for example Ephestia spp. (flour moths),Anthrenus spp. (carpet beetles), Tribolium spp. (flour beetles),Sitophilus spp. (grain weevils) or Acarus spp. (mites).

In the control of cockroaches, ants or termites or similar arthropodpests in infested domestic or industrial premises or in the control ofmosquito larvae in waterways, wells, reservoirs or other running orstanding water.

For the treatment of foundations, structures or soil in the preventionof the attack on building by termites, for example, Reticulitermes spp.,Heterotermes spp., Coptotermes spp.

In agriculture against adults, larvae and eggs of Lepidoptera(butterflies and moths), e.g. Heliothis spp. such as Heliothis virescens(tobacco budworm), Heliothis armigera and Heliothis zea. Against adultsand larvae of Coleoptera (beetles) e.g. Anthonomus spp. e.g. grandis(cotton boll weevil), Leptinotarsa decemlineata (Colorado potatobeetle), Diabrotica spp. (corn rootworms). Against Heteroptera(Hemiptera and Homoptera) e.g. Psylla spp., Bemisia spp., Trialeurodesspp., Aphis spp., Myzus spp., Megoura viciae, Phylloxera spp.,Nephotettix spp. (rice leaf hoppers), Nilaparvata spp. Against Dipterae.g. Musca spp. Against Thysanoptera such as Thrips tabaci. AgainstOrthoptera such as Locusta and Schistocerca spp., (locusts and crickets)e.g. Gryllus spp., and Acheta spp. for example, Blatta orientalis,Periplaneta americana, Blatella germanica, Locusta migratoriamigratorioides, and Schistocerca gregaria. Against Collembola e.g.Periplaneta spp. and Blatella spp. (roaches).

Against arthropods of agricultural significance such as Acari (mites)e.g. Tetranychus spp., and Panonychus spp.

Against nematodes which attack plants or trees of importance toagriculture, forestry or horticulture either directly or by spreadingbacterial, viral, mycoplasma or fungal diseases of the plants. Forexample root-knot nematodes such as Meloidogyne spp. (e.g. M.incognita).

In the field of veterinary medicine or livestock husbandry or in themaintenance of public health against arthropods which are parasiticinternally or externally upon vertebrates, particularly warm-bloodedvertebrates, for example domestic animals, e.g. cattle, sheep, goats,equines, swine, poultry, dogs or cats, for example Acarina, includingticks (e.g. soft-bodied ticks including Argasidae spp. e.g. Argas spp.and Ornithodorus spp. (e.g. Ornithodorus moubata); hard-bodied ticksincluding Ixodidae spp., e.g. Boophilus spp. e.g. Boophilus microplus,Rhipicephalus spp. e.g. Rhipicephalus appendiculatus and Rhipicephalussanguineus; mites (e.g. Damalinia spp.); fleas (e.g. Ctenocephalidesspp. e.g. Ctenocephalides felis (cat flea) and Ctenocephalides canis(dog flea)); lice e.g. Menopon spp.; Diptera (e.g. Aedes spp., Anophelesspp., Musca spp., Hypoderma spp.); Hemiptera.; Dictyoptera (e.g.Periplaneta spp., Blatella spp.); Hymenoptera; for example againstinfections of the gastro-intestinal tract caused by parasitic nematodeworms, for example members of the family Trichostrongylidae.

In a preferred aspect of the invention the compounds of formula (I) areused for the control of parasites of animals. Preferably the animal tobe treated is a domestic companion animal such as a dog or a cat.

In a further aspect of the invention the compounds of formula (I) orsalts or compositions thereof are used for the preparation of aveterinary medicament.

A further feature of the invention thus relates to the use of a compoundof formula (I) or a salt thereof, or of a composition thereof, for thecontrol of pests.

In practical use for the control of arthropods, especially insects ormites, or helminths, especially nematode pests of plants, a method, forexample, comprises applying to the plants or to the medium in which theygrow an effective amount of a compound of the invention. For such amethod, the compound of the invention is generally applied to the locusin which the arthropod or nematode infestation is to be controlled at aneffective rate in the range of about 2 g to about 1 kg of the activecompound per hectare of locus treated. Under ideal conditions, dependingon the pest to be controlled, a lower rate may offer adequateprotection. On the other hand, adverse weather conditions, resistance ofthe pest or other factors may require that the active ingredient be usedat higher rates. The optimum rate depends usually upon a number offactors, for example, the type of pest being controlled, the type or thegrowth stage of the infested plant, the row spacing or also the methodof application. Preferably an effective rate range of the activecompound is from about 10 g/ha to about 400 g/ha, more preferably fromabout 50 g/ha to about 200 g/ha.

When a pest is soil-borne, the active compound generally in a formulatedcomposition, is distributed evenly over the area to be treated (ie, forexample broadcast or band treatment) in any convenient manner and isapplied at rates from about 10 g/ha to about 400 g ai/ha, preferablyfrom about 50 g/ha to about 200 g ai/ha. When applied as a root dip toseedlings or drip irrigation to plants the liquid solution or suspensioncontains from about 0.075 to about 1000 mg ai/l, preferably from about25 to about 200 mg ai/l. Application may be made, if desired, to thefield or crop-growing area generally or in close proximity to the seedor plant to be protected from attack. The compound of the invention canbe washed into the soil by spraying with water over the area or can beleft to the natural action of rainfall. During or after application, theformulated compound can, if desired, be distributed mechanically in thesoil, for example by ploughing, disking, or use of drag chains.Application can be prior to planting, at planting, after planting butbefore sprouting has taken place, or after sprouting.

The compound of the invention and methods of control of pests therewithare of particular value in the protection of field, forage, plantation,glasshouse, orchard or vineyard crops, of ornamentals, or of plantationor forest trees, for example: cereals (such as wheat or rice), cotton,vegetables (such as peppers), field crops (such as sugar beets, soybeansor oil seed rape), grassland or forage crops (such as maize or sorghum),orchards or groves (such as of stone or pit fruit or citrus), ornamentalplants, flowers or vegetables or shrubs under glass or in gardens orparks, or forest trees (both deciduous and evergreen) in forests,plantations or nurseries.

They are also valuable in the protection of timber (standing, felled,converted, stored or structural) from attack, for example, by sawfliesor beetles or termites. They have applications in the protection ofstored products such as grains, fruits, nuts, spices or tobacco, whetherwhole, milled or compounded into products, from moth, beetle, mite orgrain weevil attack. Also protected are stored animal products such asskins, hair, wool or feathers in natural or converted form (e.g. ascarpets or textiles) from moth or beetle attack as well as stored meat,fish or grains from beetle, mite or fly attack.

Additionally, the compound of the invention and methods of use thereofare of particular value in the control of arthropods or helminths whichare injurious to, or spread or act as vectors of diseases domesticanimals, for example those hereinbefore mentioned, and more especiallyin the control of ticks, mites, lice, fleas, midges, or biting, nuisanceor myiasis flies. The compounds of the invention are particularly usefulin controlling arthropods or helminths which are present inside domestichost animals or which feed in or on the skin or suck the blood of theanimal, for which purpose they may be administered orally, parenterally,percutaneously or topically.

The compositions hereinafter described for application to growing cropsor crop growing loci or as a seed dressing may, in general,alternatively be employed in the protection of stored products,household goods, property or areas of the general environment. Suitablemeans of applying the compounds of the invention include:

-   to growing crops as foliar sprays (for example as an in-furrow    spray), dusts, granules, fogs or foams or also as suspensions of    finely divided or encapsulated compositions as soil or root    treatments by liquid drenches, dusts, granules, smokes or foams; to    seeds of crops via application as seed dressings, e.g. by liquid    slurries or dusts;-   to animals infested by or exposed to infestation by arthropods or    helminths, by parenteral, oral or topical application of    compositions in which the active ingredient exhibits an immediate    and/or prolonged action over a period of time against the arthropods    or helminths, for example by incorporation in feed or suitable    orally-ingestible pharmaceutical formulations, edible baits, salt    licks, dietary supplements, pour-on formulations, sprays, baths,    dips, showers, jets, dusts, greases, shampoos, creams, wax smears or    livestock self-treatment systems;-   to the environment in general or to specific locations where pests    may lurk, including stored products, timber, household goods, or    domestic or industrial premises, as sprays, fogs, dusts, smokes,    wax-smears, lacquers, granules or baits, or in tricklefeeds to    waterways, wells, reservoirs or other running or standing water.

The compounds of formula (I) are particularly useful for the control ofparasites of animals when applied orally, and in a further preferredaspect of the invention the compounds of formula (I) are used for thecontrol of parasites of animals by oral application. The compounds ofthe formula (I) or salts thereof may be administered before, during orafter meals. The compounds of the formula (I) or salts thereof may bemixed with a carrier and/or foodstuff.

The compound of the formula (I) or salt thereof is administered orallyin a dose to the animal in a dose range generally from 0.1 to 500 mg/kgof the compound of the formula (I) or salt thereof per kilogram ofanimal body weight (mg/kg).

The frequency of treatment of the animal, preferably the domestic animalto be treated by the compound of the formula (I) or salt thereof isgenerally from about once per week to about once per year, preferablyfrom about once every two weeks to once every three months.

The compounds of the invention may be administered most advantageouslywith another parasiticidally effective material, such as anendoparasiticide, and/or an ectoparasiticide, and/or anendectoparasiticide. For example, such compounds include macrocycliclactones such as avermectins or milbemycins e.g., ivermectin, pyratel oran insect growth regulator such as lufenuron or methoprene.

The compounds of the formula (I) can also be employed for controllingharmful organisms in crops of known genetically engineered plants orgenetically engineered plants yet to be developed. As a rule, thetransgenic plants are distinguished by especially advantageousproperties, for example by resistances to particular crop protectionagents, resistances to plant diseases or pathogens of plant diseases,such as particular insects or microorganisms such as fungi, bacteria orviruses. Other particular properties concern, for example, the harvestedmaterial with regard to quantity, quality, storage properties,composition and specific constituents. Thus, transgenic plants are knownwhere the starch content is increased, or the starch quality is altered,or where the harvested material has a different fatty acid composition.

The use in economically important transgenic crops of useful plants andornamentals is preferred, for example of cereals such as wheat, barley,rye, oats, millet, rice, cassava and maize or else crops of sugar beet,cotton, soya, oilseed rape, potatoes, tomatoes, peas and other types ofvegetables.

When used in transgenic crops, in particular those which haveresistances to insects, effects are frequently observed, in addition tothe effects against harmful organisms to be observed in other crops,which are specific for application in the transgenic crop in question,for example an altered or specifically widened spectrum of pests whichcan be controlled, or altered application rates which may be employedfor application.

The invention therefore also relates to the use of compounds of theformula (I) for controlling harmful organisms in transgenic crop plants.

According to a further feature of the present invention there isprovided a pesticidal composition comprising one or more compounds ofthe invention as defined above, in association with, and preferablyhomogeneously dispersed in one or more compatible pesticidallyacceptable diluents or carriers and/or surface active agents [i.e.diluents or carriers and/or surface active agents of the type generallyaccepted in the art as being suitable for use in pesticidal compositionsand which are compatible with compounds of the invention].

In practice, the compounds of the invention most frequently form partsof compositions. These compositions can be employed to controlarthropods, especially insects, or plant nematodes or mites. Thecompositions may be of any type known in the art suitable forapplication to the desired pest in any premises or indoor or outdoorarea. These compositions contain at least one compound of the inventionas the active ingredient in combination or association with one or moreother compatible components which are for example, solid or liquidcarriers or diluents, adjuvants, surface-active-agents, or the likeappropriate for the intended use and which are agronomically ormedicinally acceptable. These compositions, which may be prepared by anymanner known in the art, likewise form a part of this invention.

The compounds of the invention, in their commercially availableformulations and in the use forms prepared from these formulations maybe present in mixtures with other active substances such asinsecticides, attractants, sterilants, acaricides, nematicides,fungicides, growth regulatory substances or herbicides.

The pesticides include, for example, phosphoric esters, carbamates,carboxylic esters, formamidines, tin compounds and materials produced bymicroorganisms.

Preferred components in mixtures are:

-   1. from the group of the phosphorus compounds acephate,    azamethiphos, azinphos-ethyl, azinphos-methyl, bromophos,    bromophos-ethyl, cadusafos (F-67825), chlorethoxyphos,    chlorfenvinphos, chlormephos, chlorpyrifos, chlorpyrifos-methyl,    demeton, demeton-S-methyl, demeton-S-methyl sulfone, dialifos,    diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, EPN,    ethion, ethoprophos, etrimfos, famphur, fenamiphos, fenitriothion,    fensulfothion, fenthion, flupyrazofos, fonofos, formothion,    fosthiazate, heptenophos, isazophos, isothioate, isoxathion,    malathion, methacrifos, methamidophos, methidathion, salithion,    mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl,    parathion, parathion-methyl, phenthoate, phorate, phosalone,    phosfolan, phosphocarb (BAS-301), phosmet, phosphamidon, phoxim,    pirimiphos, pirimiphos-ethyl, pirimiphos-methyl, profenofos,    propaphos, proetamphos, prothiofos, pyraclofos, pyridapenthion,    quinalphos, sulprofos, temephos, terbufos, tebupirimfos,    tetrachlorvinphos, thiometon, triazophos, trichlorphon, vamidothion;-   2. from the group of the carbamates alanycarb (OK-135), aldicarb,    2-sec-butylphenyl methylcarbamate (BPMC), carbaryl, carbofuran,    carbosulfan, cloethocarb, benfuracarb, ethiofencarb, furathiocarb,    HCN-801, isoprocarb, methomyl, 5-methyl-m-cumenylbutyryl    (methyl)carbamate, oxamyl, pirimicarb, propoxur, thiodicarb,    thiofanox,    1-methylthio(ethylideneamino)-N-methyl-N-(morpholinothio)carbamat    (UC 51717), triazamate;-   3. from the group of the carboxylic esters acrinathrin, allethrin,    alphametrin, 5-benzyl-3-furylmethyl (E)-    (1R)-cis-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate,    beta-cyfluthrin, alpha-cypermethrin, beta-cypermethrin,    bioallethrin, bioallethrin ((S)-cyclopentylisomer), bioresmethrin,    bifenthrin, (RS)-1-cyano-1-(6-phenoxy-2-pyridyl)methyl    (1RS)-trans-3-(4-tert-butylphenyl)-2,2-dimethylcyclopropanecarboxylate    (NCI 85193), cycloprothrin, cyfluthrin, cyhalothrin, cythithrin,    cypermethrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate,    fenfluthrin, fenpropathrin, fenvalerate, flucythrinate, flumethrin,    fluvalinate (D isomer), imiprothrin (S-41311), lambda-cyhalothrin,    perrnethrin, phenothrin (® isomer), prallethrin, pyrethrins (natural    products), resmethrin, tefluthrin, tetramethrin, theta-cypermethrin,    tralomethrin, transfluthrin, zeta-cypermethrin (F-56701);-   4. from the group of the amidines amitraz, chlordimeform;-   5. from the group of the tin compounds cyhexatin, fenbutatin oxide;-   6. others abamectin, ABG-9008, acetamiprid, acequinocyl, Anagrapha    falcitera, AKD-1022, AKD-3059, ANS-118, azadirachtin, Bacillus    thuringiensis, Beauveria bassianea, bensultap, bifenazate,    binapacryl, BJL-932, bromopropylate, BTG-504, BTG-505, buprofezin,    camphechlor, cartap, chlorobenzilate, chlorfenapyr, chlorfluazuron,    2-(4-chlorophenyl)-4,5-diphenylthiophene (UBI-T 930),    chlorfentezine, chlorproxyfen, chromafenozide, clothianidine,    2-naphthylmethyl cyclopropanecarboxylate (Ro12-0470), cyromazin,    diacloden (thiamethoxam), diafenthiuron, DBI-3204, ethyl    2-chloro-N-(3,5-dichloro-4-(1,1,2,3,3,3-hexafluoro-1-propyloxy)phenyl)carbamoyl)-2-carboximidate,    DDT, dicofol, diflubenzuron,    N-(2,3-dihydro-3-methyl-1,3-thiazol-2-ylidene)-2,4-xylidine,    dihydroxymethyidihydroxypyrrolidine, dinobuton, dinocap, diofenolan,    emamectin benzoate, endosulfan, ethiprole (sulfethiprole),    ethofenprox, etoxazole, fenazaquin, fenoxycarb, fipronil, flonicamid    (IKI-220), fluazuron, flumite (flufenzine, SZI-121),    2-fluoro-5-(4-(4-ethoxyphenyl)-4-methyl-1-pentyl)diphenyl ether (MTI    800), granulosis and nuclear polyhedrosis viruses, fenpyroximate,    fenthiocarb, fluacrypyrim, flubenzimine, flubrocythrinate,    flucycloxuron, flufenoxuron, flufenzine, flufenprox, fluproxyfen,    gamma-HCH, halfenozide, halofenprox, hexaflumuron (DE_(—)473),    hexythiazox, HOI-9004, hydramethyinon (AC 217300), indoxacarb,    ivermectin, L-14165, imidacloprid, indoxacarb (DPX-MP062), kanemite    (AKD-2023), lufenuron, M-020, M-020, methoxyfenozide, milbemectin,    NC-196, neemgard, nidinoterfuran, nitenpyram,    2-nitromethyl-4,5-dihydro-6H-thiazine (DS 52618),    2-nitromethyl-3,4-dihydrothiazole (SD 35651),    2-nitromethylene-1,2-thiazinan-3-ylcarbamaldehyde (WL 108477),    novaluron, pirydaryl, propargite, protrifenbute, pymethrozine,    pyridaben, pyrimidifen, pyriproxyfen, NC-196, NC-1111, NNI-9768,    novaluron (MCW-275), OK-9701, OK-9601, OK-9602, OK-9802, R-195,    RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601, silafluofen,    silomadine (CG-177), spinosad, spirodiclofen, SU-9118, tebufenozide,    tebufenpyrad, teflubenzuron, tetradifon, tetrasul, thiacloprid,    thiocyclam, thiamethoxam, tolfenpyrad, triazamate, triethoxyspinosyn    A, triflumuron, verbutin, vertalec (mykotal), YI-5301.

The abovementioned components for combinations are known activesubstances, many of which are described in Ch. R Worthing, S. B. Walker,The Pesticide Manual, 12^(th) Edition, British Crop Protection Council,Farnham 2000.

The effective use doses of the compounds employed in the invention canvary within wide limits, particularly depending on the nature of thepest to be eliminated or degree of infestation, for example, of cropswith these pests. In general, the compositions according to theinvention usually contain about 0.05 to about 95% (by weight) of one ormore active ingredients according to the invention, about 1 to about 95%of one or more solid or liquid carriers and, optionally, about 0.1 toabout 50% of one or more other compatible components, such assurface-active agents or the like.

In the present account, the term “carer” denotes an organic or inorganicingredient, natural or synthetic, with which the active ingredient iscombined to facilitate its application, for example, to the plant, toseeds or to the soil. This carrier is therefore generally inert and itmust be acceptable (for example, agronomically acceptable, particularlyto the treated plant).

The carrier may be a solid, for example, clays, natural or syntheticsilicates, silica, resins, waxes, solid fertilizers (for exampleammonium salts), ground natural minerals, such as kaolins, clays, talc,chalk, quartz, attapulgite, montmorillonite, bentonite or diatomaceousearth, or ground synthetic minerals, such as silica, alumina, orsilicates especially aluminium or magnesium silicates. As solid carriersfor granules the following are suitable: crushed or fractionated naturalrocks such as calcite, marble, pumice, sepiolite and dolomite; syntheticgranules of inorganic or organic meals; granules of organic materialsuch as sawdust, coconut shells, corn cobs, corn husks or tobaccostalks; kieselguhr, tricalcium phosphate, powdered cork, or absorbentcarbon black; water soluble polymers, resins, waxes; or solidfertilizers. Such solid compositions may, if desired, contain one ormore compatible wetting, dispersing, emulsifying or colouring agentswhich, when solid, may also serve as a diluent.

The carrier may also be liquid, for example: water; alcohols,particularly butanol or glycol, as well as their ethers or esters,particularly methylglycol acetate; ketones, particularly acetone,cyclohexanone, methylethyl ketone, methylisobutylketone, or isophorone;petroleum fractions such as paraffinic or aromatic hydrocarbons,particularly xylenes or alkyl naphthalenes; mineral or vegetable oils;aliphatic chlorinated hydrocarbons, particularly trichloroethane ormethylene chloride; aromatic chlorinated hydrocarbons, particularlychlorobenzenes; water-soluble or strongly polar solvents such asdimethylformamide, dimethyl sulphoxide, or N-methylpyrrolidone;liquefied gases; or the like or a mixture thereof.

The surface-active agent may be an emulsifying agent, dispersing agentor wetting agent of the ionic or non-ionic type or a mixture of suchsurface-active agents. Amongst these are e.g., salts of polyacrylicacids, salts of lignosulphonic acids, salts of phenolsulphonic ornaphthalenesulphonic acids, polycondensates of ethylene oxide with fattyalcohols or fatty acids or fatty esters or fatty amines, substitutedphenols (particularly alkylphenols or arylphenols), salts ofsulphosuccinic acid esters, taurine derivatives (particularlyalkyltaurates), phosphoric esters of alcohols or of polycondensates ofethylene oxide with phenols, esters of fatty acids with polyols, orsulphate, sulphonate or phosphate functional derivatives of the abovecompounds. The presence of at least one surface-active agent isgenerally essential when the active ingredient and/or the inert carrierare only slightly water soluble or are not water soluble and the carrieragent of the composition for application is water.

Compositions of the invention may further contain other additives suchas adhesives or colorants. Adhesives such as carboxymethylcellulose ornatural or synthetic polymers in the form of powders, granules orlattices, such as arabic gum, polyvinyl alcohol or polyvinyl acetate,natural phospholipids, such as cephalins or lecithins, or syntheticphospholipids can be used in the formulations. It is possible to usecolorants such as inorganic pigments, for example: iron oxides, titaniumoxides or Prussian Blue; organic dyestuffs, such as alizarin dyestuffs,azo dyestuffs or metal phthalocyanine dyestuffs; or trace nutrients suchas salts of iron, manganese, boron, copper, cobalt, molybdenum or zinc.

For their agricultural application, the compounds of the invention aretherefore generally in the form of compositions, which are in varioussolid or liquid forms. Solid forms of compositions which can be used aredusting powders (with a content of the compound of the invention,ranging up to 80%), wettable powders or granules (including waterdispersible granules), particularly those obtained by extrusion,compacting, impregnation of a granular carrier, or granulation startingfrom a powder (the content of the compound of the invention, in thesewettable powders or granules being between about 0.5 and about 80%).Solid homogenous or heterogenous compositions containing one or morecompounds of the invention, for example granules, pellets, briquettes orcapsules, may be used to treat standing or running water over a periodof time. A similar effect may be achieved using trickle or intermittentfeeds of water dispersible concentrates as described herein. Liquidcompositions, for example, include aqueous or non-aqueous solutions orsuspensions (such as emulsifiable concentrates, emulsions, flowables,dispersions, or solutions) or aerosols. Liquid compositions alsoinclude, in particular, emulsifiable concentrates, dispersions,emulsions, flowables, aerosols, wettable powders (or powder forspraying), dry flowables or pastes as forms of compositions which areliquid or intended to form liquid compositions when applied, for exampleas aqueous sprays (including low and ultra-low volume) or as fogs oraerosols. Liquid compositions, for example, in the form of emulsifiableor soluble concentrates most frequently comprise about 5 to about 80% byweight of the active ingredient, while the emulsions or solutions whichare ready for application contain, in their case, about 0.01 to about20% of the active ingredient. Besides the solvent, the emulsifiable orsoluble concentrates may contain, when required, about 2 to about 50% ofsuitable additives, such as stabilizers, surface-active agents,penetrating agents, corrosion inhibitors, colorants or adhesives.Emulsions of any required concentration, which are particularly suitablefor application, for example, to plants, may be obtained from theseconcentrates by dilution with water. These compositions are includedwithin the scope of the compositions which may be employed in thepresent invention. The emulsions may be in the form of water-in-oil oroil-in-water type and they may have a thick consistency.

The liquid compositions of this invention may, in addition to normalagricultural use applications be used for example to treat substrates orsites infested or liable to infestation by arthropods (or other pestscontrolled by compounds of this invention) including premises, outdooror indoor storage or processing areas, containers or equipment orstanding or running water.

All these aqueous dispersions or emulsions or spraying mixtures can beapplied, for example, to crops by any suitable means, chiefly byspraying, at rates which are generally of the order of about 100 toabout 1,200 liters of spraying mixture per hectare, but may be higher orlower (eg. low or ultra-low volume) depending upon the need orapplication technique. The compound or compositions according to theinvention are conveniently applied to vegetation and in particular toroots or leaves having pests to be eliminated. Another method ofapplication of the compounds or compositions according to the inventionis by chemigation, that is to say, the addition of a formulationcontaining the active ingredient to irrigation water. This irrigationmay be sprinkler irrigation for foliar pesticides or it can be groundirrigation or underground irrigation for soil or for systemicpesticides.

The concentrated suspensions, which can be applied by spraying, areprepared so as to produce a stable fluid product which does not settle(fine grinding) and usually contain from about 10 to about 75% by weightof active ingredient, from about 0.5 to about 30% of surface-activeagents, from about 0.1 to about 10% of thixotropic agents, from about 0to about 30% of suitable additives, such as anti-foaming agents,corrosion inhibitors, stabilizers, penetrating agents, adhesives and, asthe carrier, water or an organic liquid in which the active ingredientis poorly soluble or insoluble Some organic solids or inorganic saltsmay be dissolved in the carrier to help prevent settling or asantifreezes for water.

The wettable powers (or powder for spraying) are usually prepared sothat they contain from about 10 to about 80% by weight of activeingredient, from about 20 to about 90% of a solid carrier, from about 0to about 5% of a wetting agent, from about 3 to about 10% of adispersing agent and, when necessary, from about 0 to about 80% of oneor more stabilizers and/or other additives, such as penetrating agents,adhesives, anti-caking agents, colorants, or the like. To obtain thesewettable powders, the active ingredient is thoroughly mixed in asuitable blender with additional substances which may be impregnated onthe porous filler and is ground using a mill or other suitable grinder.This produces wettable powders, the wettability and the suspendabilityof which are advantageous. They may be suspended in water to give anydesired concentration and this suspension can be employed veryadvantageously in particular for application to plant foliage.

The “water dispersible granules (WG)” (granules which are readilydispersible in water) have compositions which are substantially close tothat of the wettable powders. They may be prepared by granulation offormulations described for the wettable powders, either by a wet route(contacting finely divided active ingredient with the inert filler and alittle water, e.g. 1 to 20% by weight, or with an aqueous solution of adispersing agent or binder, followed by drying and screening), or by adry route (compacting followed by grinding and screening).

The rates and concentrations of the formulated compositions may varyaccording to the method of application or the nature of the compositionsor use thereof. Generally speaking, the compositions for application tocontrol arthropod or plant nematode pests usually contain from about0.00001% to about 95%, more particularly from about 0.0005% to about 50%by weight of one or more compounds of the invention, or of total activeingredients (that is to say the compounds of the invention, togetherwith other substances toxic to arthropods or plant nematodes,synergists, trace elements or stabilizers). The actual compositionsemployed and their rate of application will be selected to achieve thedesired effect(s) by the farmer, livestock producer, medical orveterinary practitioner, pest control operator or other person skilledin the art.

Solid or liquid compositions for application topically to animals,timber, stored products or household goods usually contain from about0.00005% to about 90%, lo more particularly from about 0.001% to about10%, by weight of one or more compounds of the invention. Foradministration to animals orally or parenterally, includingpercutaneously solid or liquid compositions, these normally contain fromabout 0.1% to about 90% by weight of one or more compounds of theinvention. Medicated feedstuffs normally contain from about 0.001% toabout 3% by weight of is one or more compounds of the invention.Concentrates or supplements for mixing with feedstuffs normally containfrom about 5% to about 90%, preferably from about 5% to about 50%, byweight of one or more compounds of the invention. Mineral salt licksnormally contain from about 0.1% to about 10% by weight of one or morecompounds of formula (I) or pesticidally acceptable salts thereof.

Dusts or liquid compositions for application to livestock, goods,premises or outdoor areas may contain from about 0.0001% to about 15%,more especially from about 0.005% to about 2.0%, by weight, of one ormore compounds of the invention. Suitable concentrations in treatedwaters are between about 0.0001 ppm and about 20 ppm, more particularlyabout 0.001 ppm to about 5.0 ppm. of one or more compounds of theinvention, and may be used therapeutically in fish farming withappropriate exposure times. Edible baits may contain from about 0.01% toabout 5%, preferably from about 0.01% to about 1.0%, by weight, of oneor more compounds of the invention.

When administered to vertebrates parenterally, orally or by percutaneousor other means, the dosage of compounds of the invention, will dependupon the species, age, or health of the vertebrate and upon the natureand degree of its actual or potential infestation by arthropod orhelminth pests. A single dose of about 0.1 to about 100 mg, preferablyabout 2.0 to about 20.0 mg, per kg body weight of the animal or doses ofabout 0.01 to about 20.0 mg, preferably about 0.1 to about 5.0 mg, perkg body weight of the animal per day, for sustained medication, aregenerally suitable by oral or parenteral administration. By use ofsustained release formulations or devices, the daily doses required overa period of months may be combined and administered to animals on asingle occasion.

The following composition EXAMPLES 2A-2M illustrate compositions for useagainst arthropods, especially mites or insects, or plant nematodes,which comprise, as active ingredient, compounds of the invention, suchas those described in preparative examples. The compositions describedin EXAMPLES 2A-2M can each be diluted to give a sprayable compositon atconcentrations suitable for use in the field. Generic chemicaldescriptions of the ingredients (for which all of the followingpercentages are in weight percent), used in the composition EXAMPLES2A-2M exemplified below, are as follows:

Trade Name Chemical Description Ethylan BCP Nonylphenol ethylene oxidecondensate Soprophor BSU Tristyrylphenol ethylene oxide condensateArylan CA A 70% w/v solution of calcium dodecylbenzenesulfonate Solvesso150 Light C₁₀ aromatic solvent Arylan S Sodium dodecylbenzenesulfonateDarvan NO₂ Sodium lignosulphonate Celite PF Synthetic magnesium silicatecarrier Sopropon T36 Sodium salts of polycarboxylic acids Rhodigel 23Polysaccharide xanthan gum Bentone 38 Organic derivative of magnesiummontmorillonite Aerosil Microfine silicon dioxide

Example 2A

A water soluble concentrate is prepared with the composition as follows:

Active ingredient  7% Ethylan BCP 10% N-methylpyrrolidone 83%

To a solution of Ethylan BCP dissolved in a portion ofN-methylpyrrolidone is added the active ingredient with heating andstirring until dissolved. The resulting solution is made up to volumewith the remainder of the solvent.

Example 2B

An emulsifiable concentrate (EC) is prepared with the composition asfollows:

Active ingredient 25% (max) Soprophor BSU 10% Arylan CA 5%N-methylpyrrolidone 50% Solvesso 150 10%

The first three components are dissolved in N-methylpyrrolidone and tothis is then added the Solvesso 150 to give the final volume.

Example 2C

A wettable powder (WP) is prepared with the composition as follows:

Active ingredient 40% Arylan S  2% Darvan NO₂  5% Celite PF 53%

The ingredients are mixed and ground in a hammer-mill to a powder with aparticle size of less than 50 microns.

Example 2D

An aqueous-flowable formulation is prepared with the composition asfollows:

Active ingredient 40.00%  Ethylan BCP 1.00% Sopropon T360. 0.20%Ethylene glycol 5.00% Rhodigel 230. 0.15% Water 53.65% 

The ingredients are intimately mixed and are ground in a bead mill untila mean particle size of less than 3 microns is obtained.

Example 2E

An emulsifiable suspension concentrate is prepared. with the compositionas follows:

Active ingredient 30.0% Ethylan BCP 10.0% Bentone 38  0.5% Solvesso 15059.5%

The ingredients are intimately mixed and ground in a beadmill until amean particle size of less than 3 microns is obtained.

Example 2F

A water dispersible granule is prepared with the composition as follows:

Active ingredient 30% Darvan No 2 15% Arylan S  8% Celite PF 47%

The ingredients are mixed, micronized in a fluid-energy mill and thengranulated in a rotating pelletizer by spraying with water (up to 10%).The resulting granules are dried in a fluid-bed drier to remove excesswater.

Example 2G

Active ingredient  1 to 10% Talc powder-superfine 99 to 90%

The ingredients are intimately mixed and further ground as necessary toachieve a fine powder. This powder may be appplied to a locus ofarthropod infestation, for example refuse dumps, stored products orhousehold goods or animals infested by, or at risk of infestation by,arthropods to control the arthropods by oral ingestion. Suitable meansfor distributing the dusting powder to the locus of arthropodinfestation include mechanical blowers, handshakers or livestock selftreatment devices.

Example 2H

An edible bait is prepared with the composition as follows:

Active ingredient  0.1 to 1.0% Wheat flour 80% Molasses 19.9 to 19%

The ingredients are intimately mixed and formed as required into a baitform. This edible bait may be distributed at a locus, for exampledomestic or industrial premises, e.g. kitchens, hospitals or stores, oroutdoor areas, infested by arthropods, for example ants, locusts,cockroaches or flies, to control the lo arthropods by oral ingestion.

Example 2I

A solution formulation is prepared with a composition as follows:

Active ingredient 15% Dimethyl sulfoxide 85%

The active ingredient is dissolved in dimethyl sulfoxide with mixing andor heating as required. This solution may be applied percutaneously as apour-on application to domestic animals infested by arthropods or, aftersterilization by filtration through a polytetrafluoroethylene membrane(0.22 micrometer pore size), by parenteral injection, at a rate ofapplication of from 1.2 to 12 ml of solution per 100 kg of animal bodyweight.

Example 2J

A wettable powder is prepared with the composition as follows:

Active ingredient 50% Ethylan BCP  5% Aerosil  5% Celite PF 40%

The Ethylan BCP is absorbed onto the Aerosil which is then mixed withthe other ingredients and ground in a hammer-mill to give a wettablepowder, which may be diluted with water to a concentration of from0.001% to 2% by weight of the active compound and applied to a locus ofinfestation by arthropods, for example, dipterous larvae or plantnematodes, by spraying, or to domestic animals infested by, or at riskof infection by arthropods, by spraying or dipping, or by oraladministration in drinking water, to control the arthropods.

Example 2K

A slow release bolus composition is formed from granules containing thefollowing components in varying percentages(similar to those describedfor the previous compositions) depending upon need:

-   -   Active ingredient    -   Density agent    -   Slow-release agent    -   Binder

The intimately mixed ingredients are formed into granules which arecompressed into a bolus with a specific gravity of 2 or more. This canbe administered orally to ruminant domestic animals for retention withinthe reticulo-rumen to give a continual slow release of active compoundover an extended period of time to control infestation of the ruminantdomestic animals by arthropods.

Example 2L

A slow release composition in the form of granules, pellets, brickettesor the like can be prepared with compositions as follows:

The components are blended and then formed into suitable shapes bymelt-extrusion or molding. These composition are useful, for example,for addition to standing water or for fabrication into collars oreartags for attachment to domestic animals to control pests by slowrelease.

Active ingredient 0.5 to 25% Polyvinyl chloride 75 to 99.5% Dioctylphthalate (plasticizer)

Example 2M

A water dispersible granule is prepared with the composition as follows:

Active ingredient 85% (max) Polyvinylpyrrolidone 5% Attapulgite clay 6%Sodium lauryl sulfate 2% Glycerine 2%

The ingredients are mixed as a 45% slurry with water and wet milled to aparticle size of 4 microns, then spray-dried to remove water.

Methods of Pesticidal Use

The following representative test procedure, using compounds of theinvention, was conducted to determine the parasiticidal activity ofcompounds of the invention.

METHOD A: Screening method to test systemicity of compounds againstCtenocephalides felis (Cat flea)

A test container was filled with 10 adults of Ctenocephalides felis. Aglass cylinder was closed on one end with parafilm and placed on top ofthe test container. The test compound solution was then pipetted intobovine blood and added to the glass cylinder. The treatedCtenocephalides felis were held in this artificial dog test (blood 37°C., 40-60% relative humidity; Ctenocephalides felis 20-22° C., 40-60%relative humidity) and assessment performed at 24 and 48 hours afterapplication. Compound numbers 6, 30, 39, 51, 54, 57, 63, 69, 72, 84, 90and 93 gave at least 80% control of Ctenocephalides felis at a testconcentration of 500 ppm or less.

1. A compound of formula (I):

wherein: R¹ is CN or CSNH₂; W is C-halogen; R² is hydrogen or halogen;R³ is (C₁-C₃)-haloalkyl, (C₁-C₃)-haloalkoxy or SF₅; R⁴ is hydrogen,CO₂—(C₁-C₆)-alkyl, CO₂—(C₃-C₆)-alkenyl, CO₂—(C₃-C₆)-alkynyl,CO₂—(CH₂)_(m)R⁷ or SO₂R⁸; or (C₁-C₆)-alkyl unsubstituted or substitutedby one or more radicals selected from the group consisting of halogen,(C₁-C₆)-alkoxy, (C₁-C₆)-haloalkoxy, OH, NR⁹R¹⁰, and OR⁷; A is(C₁-C₆)-alkylene; X is C(═O), C(═S) or SO₂; Y is O, NR¹¹ or a covalentbond; R⁵is (C₃-C₆)-alkenyl, —(CH₂)_(q)R⁷ or —(CH₂)_(q)R¹²; or isC₁-C₆)-alkyl unsubstituted or substituted by one or more radicalsselected from the group consisting of halogen, (C₁-C₆)-alkoxy,(C₁-C₆)-haloalkoxy, And NR⁹R¹⁰; R⁶ is (C₁-C₆)-alkyl or(C₁-C₆)-haloalkyl; R⁷ is phenyl unsubstituted or substituted by one ormore radicals selected from the group consisting of halogen,(C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl, (C₁-C₆)-alkoxy, (C₁-C₆)-haloalkoxy,CN, NO₂, NR⁹R¹⁰ and OH; R⁸ is (C₁-C₆)-alkyl or (C₁-C₆)-haloalkyl; R⁹ andR¹⁰ are each independently H or (C₁-C₆)-alkyl R¹¹ is H or (C₁-C₆)-alkyl;R¹² is heterocyclyl; n is zero, one or two; m and q are eachindependently is zero or one; and each heterocyclyl in theabove-mentioned radicals is independently a heterocyclic radical having3 to 7 ring atoms and 1, 2 or 3 hetero atoms in the ring selected fromthe group consisting of N, O and S; or a pesticidally acceptable saltthereof.
 2. A compound or a salt thereof as claimed in claim 1 whereinR⁶ is CF₃.
 3. A compound or a salt thereof as claimed in claim 1 whereinW is C—Cl; R² is Cl; R³ is CF₃; R⁴ is hydrogen, CO₂—(C₁-C₄)-alkyl,CO₂—(C₃-C₄)-alkenyl, CO₂—(C₃-C₄)-alkynyl, CO₂—(CH₂)_(m)R⁷ or SO₂R⁸; or(C₁-C₃)-alkyl unsubstituted or substituted by one or more radicalsselected from the group consisting of halogen and (C₁-C₃)-alkoxy; A is—CH₂CH₂— or —CH₂CH₂CH₂—; X is C(═O) or SO₂; Y is O, NH or a covalentbond; R⁵ is (C₃-C₄)-alkenyl, —(CH₂)_(q)R⁷, (C₁-C₃)-alkyl or(C₁-C₃)-haloakyl; R⁶ is CF₃; each R⁷ is independently phenylunsubstituted or substituted by one or more radicals selected from thegroup consisting of halogen, (C₁-C₃)-alkyl, (C₁-C₃)-haloalkyl,(C₁-C₃)-alkoxy, (C₁-C₃)-haloalkoxy, CN, NO₂; and each R⁸ isindependently (C₁-C₃)-alkyl or (C₁-C₃)-haloalkyl.
 4. A compound or asalt thereof as claimed in claim 1 wherein W is C—Cl; R² is Cl; R³ isCF₃; R⁴ is (C₁-C₃)-alkyl; A is —CH₂CH₂— or —CH₂CH₂CH₂—; X is C(═O); Y isO, NH or a covalent bond; R⁵ is (C₃-C₄)-alkenyl, —(CH₂)_(q)R⁷,(C₁-C₃)-alkyl or (C₁-C₃)-haloalkyl; R⁶ is CF₃; R⁷ is phenylunsubstituted or substituted by one or more radicals selected from thegroup consisting of halogen, (C₁-C₃)-alkyl, (C₁-C₃)-haloalkyl,(C₁-C₃)-alkoxy, (C₁-C₃)-haloalkoxy, CN, and NO₂; and R⁸ is (C₁-C₃)-alkylor (C₁-C₃)-haloalkyl.
 5. A process for the preparation of a compound offormula (I) or a salt thereof as defined in claim 1, which processcomprises: a) when R², R³, R⁴, R⁵, R⁶, W, A and n are as defined inclaim 1, R¹ is CN, and Y and X are as defined in claim 1 with theexclusion of compounds in which —Y—X— is —NH—CO— or —NH—CS—, acylatingor sulfonylating a compound of formula (II):

wherein R², R³, R⁴, R⁶, W, A and n are as defined in formula (I), with acompound of formula (III):R⁵—Y—X-L  (III) wherein Y and X are as defined in formula (I) with theexclusion of compounds in which —Y—X— is —NH—CO— or —NH—CS—, and L is aleaving group; or b) when R¹ is CN, and R², R³, R⁴, R⁵, R⁶, W, A and nare as defined in claim 1, reacting a compound of formula (II) whereinR¹, R², R³, R⁶, W, A and n are as defined in claim 1 and —Y—X— is—NH—CO— or —NH—CS—, with an isocyanate or isothiocyanate compound offormula (IV) or (V):R⁵—N═C═O  (IV)R⁵—N═C═S  (V) wherein R⁵ is as defined in formula(I); or c) when R¹ isCN, n is 1 or 2, and R², R³, R⁴, R⁵, R⁶, W, A, X and Y are as defined inclaim 1, oxidizing a corresponding compound in which n is 0 or 1; or d)when R¹ is CSNH₂, and R², R³, R⁴, R⁵, R⁶, W, A, X, Y and n are asdefined in claim 1, reacting the corresponding compound of formula (I)wherein R¹ is CN, with an alkali or alkaline earth metal hydrosulfide,or with the reagent Ph₂PS₂; or (e) when R¹ is CSNH₂, and R², R³, R⁴, R⁵,R⁶, W, A, X, Y and n are as defined in claim 1, reacting thecorresponding compound of formula (I) wherein R¹ is CN, with abis(trialkylsilyl)sulfide, in the presence of a base; and (f) optionallyconverting a resulting compound of formula (I) into a pesticidallyacceptable salt thereof.
 6. A pesticidal composition comprising apesticidally effective amount of a compound of formula (I) or apesticidally acceptable salt thereof as defined in claim 1, inassociation with a pesticidally acceptable diluent or carrier and/orsurface active agent.
 7. A method for controlling pests at a locus whichcomprises applying to said locus a pesticidally effective amount of acompound of formula (I) or a salt thereof as claimed in claim
 1. 8. Amethod for controlling pests at a locus which comprises applying to saidlocus a pesticidally effective amount of a composition as claimed inclaim
 6. 9. A veterinary medicament comprising a pesticidally effectiveamount of a compound of formula (I) or a salt thereof as claimed inclaim 1, in association with a veterinarily acceptable diluent orcarrier and/or surface active agent.
 10. A method for the control ofpests in or on an animal which comprises administering to said animal apesticidally effective amount of a compound of formula (I) or a saltthereof as claimed in claim
 1. 11. A method for the control of pests inor on an animal which comprises administering to said animal apesticidally effective amount of a veterinary medicament as claimed inclaim
 9. 12. A compound or a salt thereof as claimed in claim 1, whereinR¹ is CN, R⁴ is CH₃, R⁶ is CF₃, A is —CH₂CH₂—, W is C—Cl, R² is Cl andR³ is CF₃.
 13. The compound or salt thereof

wherein: R¹ is CN, R⁴ is CH₃, R⁶ is CF₃, A is —CH₂CH₂—, W is C—Cl, R² isCl and R³ is CF₃; and (a) X is C(═O), Y is O, R⁵ is CH₃ and n is 1; (b)X is C(═O), Y is O, R⁵ is 4-nitrophenyl and n is 2; (c) X is C(═O), Y isa covalent bond, R⁵ is CH₃ and n is 2; (d) X is C(═O), Y is a covalentbond, R⁵ is CH₂OCH₃ and n is 2; (e) X is C(═O), Y is a covalent bond, R⁵is 4-trifluoromethylphenyl and n is 2; (f) X is C(═O), Y is a covalentbond, R⁵ is 2,6-difluorophenyl and n is 2; (g) X is C(═O), Y is acovalent bond, R⁵ is 2-fluorophenyl and n is 2; (h) X is C(═O), Y is NH,R⁵ is 4-ethoxyphenyl and n is 2; (i) X is C(═O), Y is NH, R⁵ is4-trifluoromethoxyphenyl and n is 2; (j) X is SO₂, Y is a covalent bond,R⁵ is propyl and n is 2; (k) X is SO₂, Y is a covalent bond, R⁵ is4-chlorophenyl and n is 2; or (l) X is SO₂, Y is a covalent bond, R⁵ is4-methylphenyl and n is 2.